This present invention relates generally to methods and apparatus for forming hydrogels in situ, especially during open or minimally invasive surgery. More particularly, the present invention relates to apparatus and methods for delivering two liquid components that form hydrogels upon mixing.
often during surgery, tissue may be traumatized or compromised such that it needs to be temporarily supported or isolated during the wound healing period. Materials that may be used as tissue sealants also may be used to temporarily support tissue and to seal leaks from tissue until the tissue heals. Tissue sealants that perform these functions are well known in literature and include a variety of natural and synthetic sealants including fibrin sealants, cyanoacrylate based sealants, and other synthetic sealants and polymerizable macromers.
Various types of previously known apparatus have been developed to deliver fibrin sealants, which are derived from blood-based proteins. For example, U.S. Pat. No. 5,605,541 to Holm describes apparatus and methods for applying two or more components of a fibrin sealant. That patent describes a spray head having a central gas discharge port and coaxially arranged annular ports through which respective components of the fibrin sealant are discharged. The spray head may be prone to clogging if the central gas discharge port is restricted.
U.S. Pat. No. 5,368,563 to Lonneman et al. describes a sprayer assembly having angular connecting channels through which components of a fibrin sealant are discharged to cause mixing. U.S. Pat. No. 5,341,993 to Haber et al. describes a hand held sprayer having a remotely actuated spray tip. Both of the devices described in those patents may not be suitable for spraying viscous fluids, which tend to emerge as streams rather than as fine sprays.
U.S. Pat. No. 4,001,391 to Feinstone et al. describes a method for spraying viscous and buttery fluids using a propellant and a pressurized container. The use of propellants is undesirable in medical applications due to uncertain biocompatibility of these materials.
In view of the foregoing, it would be desirable to provide apparatus and methods that enable a tissue coating comprising two or more crosslinkable fluids to be applied in situ as a spray.
It further would be desirable to provide apparatus and methods for spraying polymerizable fluids with reduced risk of clogging of the sprayer.
In view of the foregoing, it is an object of the present invention to provide apparatus and methods that enable a tissue coating comprising two or more crosslinkable fluids to be applied in situ as a spray.
It is a further object of this invention to provide apparatus and methods for spraying crosslinkable fluids with reduced risk of clogging of the sprayer.
These and other objects of the invention are accomplished by providing a sprayer capable of applying two or more viscous crosslinkable components to tissue to form a coating that adheres to the tissue surface. For example, two crosslinkable solutions, each containing one component of a co-initiating system capable of crosslinking when mixed together, may be placed in separate chambers of the sprayer. When the sprayer is activated, the emergent spray contacts tissue, resulting in mixing and crosslinking of the two solutions to form a coating (for example a hydrogel) on the tissue surface.
In a preferred embodiment, the sprayer comprises separate spray nozzles for each of two or more crosslinkable solutions, with each nozzle surrounded by a separate or common gas flow outlet. The crosslinkable solutions are stored in separate compartments, e.g., a multi-cylinder syringe, and communicated under pressure to the spray nozzles. In the presence of gas flow through the gas flow outlets, the crosslinkable solutions are atomized and mixed in the gas flow to form a spray, which may be used to coat tissue.
The crosslinkable solutions used with the apparatus may be crosslinked using either physical crosslinking, chemical crosslinking, or both. For a chemical initiation process, the two or more crosslinkable solutions may polymerize when mixed in the gas flows during spraying, thus forming an adherent coating that adheres to the tissue surface on contact. If a thermal initiating process is used, the two or more solutions may crosslink after contacting the tissue surface and warming to physiological temperatures.
Alternatively, the two or more solutions may include macromers that contain groups that demonstrate activity towards other functional groups such as amines, imines, thiols, carboxyls, isocyanates, urethanes, amides, thiocyanates, hydroxyls, etc., which may be naturally present in, on, or around tissue or may be optionally provided in the region as part of the instilled formulation required to effect the barrier.
Methods of forming tissue adherent barriers in accordance with the principles of the present invention also are provided.